The treatment of menopausal symptoms such as flashing, osteoporosis and other symptoms associated with hormone deficiency is old. Typically, the known formulations for such treatment have contained natural estrogen or other estrogenic component(s) as the only hormonal ingredient. Known formulations were designed to treat symptoms rather than to replace the physiologic deficiency that results from dysfunctional ovaries. Also known formulations were marketed without adequate dose ranging and dosed in a cyclic fashion. The administration of estrogen in a cyclic fashion was an attempt to rest the endometrium from the continuous stimulation of estrogen. This practice is questionable in that the half-life of equine estrogens can be long (lipid soluble) and the patient never falls out of therapeutic range. As a result, despite cyclic administration, the replacement of estrogen with these types of formulations containing estrogen only has led to evidence of hyperstimulation of the endometrium and, in some cases, subsequent adenocarcinoma.
To minimize the potential for hyperstimulation, 5-14 days of progestional therapy has been included on a monthly basis to slough the endometrium. As a result, the patient experiences a monthly withdrawal bleed similar to the premenopausal state. Market research with physicians indicates that the nuisance of this cyclic bleeding is the single most important reason postmenopausal females refuse or discontinue therapy. Although progestins protect against hyperstimulation, they have been associated with a negative effect on blood lipids. As opposed to estrogen's positive effect on lipids, e.g., increase HDL/lower LDL, progestin's negative effect on lipids may compromise the cardioprotective state of the premenopausal female.